Over half of all cervical cancers in the U.S. are diagnosed in unscreened or under screened women. New national guidelines identify increasing screening uptake as the number one priority for reducing cervical cancer-related morbidity and mortality. Innovative screening strategies that eliminate the need for clinic-based screening could be highly effective in improving screening compliance while maintaining high-quality care. There is growing interest in using high-risk (hr) HPV screening followed by cytology-based triage of women with hrHPV as a primary screening strategy, with studies suggesting that such a strategy could be both cost- effective and sensitive for detecting cervical neoplasia. If samples for hrHPV screening could be self-collected at home (with in-clinic follow-up of hrHPV-positive women), the need for in-clinic screening could be eliminated for a majority of women. We propose a large, pragmatic randomized controlled trial within Group Health (a large integrated health care delivery system in Washington State) to compare effectiveness of two programmatic approaches to increasing cervical cancer screening among overdue women aged 30-65 years. The first approach (control arm) is usual care at Group Health, which consists of patient- and provider-level services to promote adherence to Pap screening, and the second approach (intervention arm) includes usual care plus a mailed in-home hrHPV screening kit. Primary outcomes are early detection and treatment of cervical neoplasia and secondary outcomes are cervical cancer screening uptake, predictors of screening, and patient experiences and attitudes towards in-home hrHPV testing and follow-up of hrHPV+ results (measured through surveys and interviews). We will identify all 30 to 65 year old female enrollees who are overdue for routine Pap screening (no Pap test within the last 3.4 years). We will randomize 7,200 to in-home hrHPV screening and the remainder (~10,400) to usual care. Compared to usual care, we hypothesize that in-home hrHPV screening will enhance early detection and treatment of cervical neoplasia and improve compliance with screening. The trial will provide definitive evidence-based data on the impact of an in-home hrHPV screening program in a real-world clinical setting.